| First Author | Hara H | Year | 1997 |
| Journal | J Cereb Blood Flow Metab | Volume | 17 |
| Issue | 5 | Pages | 515-26 |
| PubMed ID | 9183289 | Mgi Jnum | J:41921 |
| Mgi Id | MGI:894635 | Doi | 10.1097/00004647-199705000-00005 |
| Citation | Hara H, et al. (1997) [3H]L-NG-nitroarginine binding after transient focal ischemia and NMDA-induced excitotoxicity in type I and type III nitric oxide synthase null mice. J Cereb Blood Flow Metab 17(5):515-26 |
| abstractText | We investigated the density and distribution of nitric oxide synthase (NOS) binding by quantitative autoradiography using [3H]L-NG-nitroarginine ([3H]L-NNA) after transient focal ischemia or intrastriatal injection of N-methyl-D-aspartate (NMDA) in wild-type (SV-129 and C57black/6) and type I (neuronal) and type III (endothelial) NOS-deficient mice. The middle cerebral artery (MCA) was occluded by an intraluminal filament for 3 h followed by 10 min to 7 days of reperfusion. Specific [3H]L-NNA binding, observed in the wild-type and type III mutant mouse at baseline, increased by 50-250% in the MCA territory during ischemia and the first 3 h of reperfusion. The density of binding sites (Bmax), but not the dissociation constant (Kd), increased significantly during the ischemic period as did type I NOS mRNA as detected by quantitative reverse transcription polymerase chain reaction. [3H]L-NNA binding after intrastriatal NMDA injection also increased by 20-230%. In the type I NOS-deficient mouse, [3H]L-NNA binding was low and only a very small increase was observed after ischemia or excitotoxicity. Under conditions of this study, [3H]L-NNA did not bind to type II NOS as there was no difference in the distribution or density of [3H]L-NNA binding in the rat spleen obtained after lipopolysaccharide treatment despite induction of NOS type II catalytic activity. Our data suggest that an ischemic/excitotoxic insult up-regulates type I NOS gene expression and [3H]L-NNA binding and that this up-regulation may play a pivotal role in the pathogenesis of ischemic/excitotoxic diseases. |
